The process of normal hematopoiesis requires the sequential coordination of many complex events. These include the interaction of stimulatory growth factors with their membrane receptors, generation of the appropriate signal followed by its transduction through the cell membrane and cytoplasm into the nucleus, and finally, DNA synthesis and cell division. Accordingly, it seems reasonable to assume that perturbations in any of these controlled events are likely to result in altered cell growth patterns and possibly in the emergence of cells with a leukemic phenotype, especially in the presence of cumulative alterations in these various components of the proliferative program. As a paradigm of this concept, our proposal centers on the investigation of the role of c-myb in normal and leukemic hematopoiesis because this gene is not only involved in cell cycle regulation, but also appears to affect the generation of the growth signal and its transduction in a cell- type specific manner.